Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: the GEMS Study.
Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n=2800) and in an independent set of dyslipidemic cases (n=716) and normolipidemic controls (n=1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).


Learning from a codesign exercise aimed at developing a navigation intervention in the general practice setting.
In this study, we aimed to describe and evaluate the codesign of an intervention in general practice setting to help address navigation problems faced by the patients from the culturally and linguistically diverse (CALD) community in Australia. An experience-based codesign (EBCD) methodology was adopted using the Double Diamond design process. Two codesign workshops were conducted online with 13 participants including patients, their caregivers, health service providers, researchers, and other stakeholders. Workshops were audio-recorded, transcribed, and thematically analyzed. The codesign participants identified several navigation problems among CALD patients such as inadequate health literacy, cultural and language barriers, and difficulties with navigating health and social services. They believed that bilingual community navigators (BCNs; lay health workers from the same language or cultural background) could help them address these problems. However, this depended on BCNs being trained and supervised, with a clear role definition and manageable workloads, and not used as an interpreter. In undertaking the codesign process, we found that pre-workshop consultations were useful to ensure engagement, especially for consumers who participated more actively in group activities with service providers after these and their own separate small group discussions during the workshop. Overall, participants identified that BCNs could offer help in addressing the problems faced by the CALD patients in accessing care in general practice setting. The codesign process provided new insights into the navigation problems faced by CALD patients in accessing care and collaboratively developed a strategy for further testing and evaluation.


A Bumper Crop of Boiling-Water-Stable Metal-Organic Frameworks from Controlled Linker Sulfuration.
The series of highly stable porous solids here feature systematic, regiospecific sulfur substitutions on the organic linkers for versatile functions. One major surprise lies in the controllable sequential reactions between sodium thiomethoxide (NaSMe) and octafluorobiphenyl-4,4'-dicarboxylic acid (H2bpdc-8F; this was readily made without precious metal catalysts). Namely, 3, 4, 6, and 8 methylthio-substitutions can be respectively achieved with regiospecificity (i.e., to produce the four molecules H2bpdc-3S5F, H2bpdc-4S4F, H2bpdc-6S2F, H2bpdc-8MS). A second surprise lies in their persistent formation of the UiO-67-type net with Zr(IV) ions, e.g., even in the case of the fully sulfurated H2bpdc-8MS. In addition to the remarkable breadth of functional control, all the Zr(IV)-based crystalline solids here are stable in boiling water (e.g., for 24 h) and in air as solventless, activated porous solids. Moreover, the thioether groups allow for convenient H2O2 oxidation to fine-tune the hydrophilicity and luminescence properties and improve proton conductivity.


Posttraumatic Pseudoarthrosis of a Clavicle Fracture in an 11-Year-Old Girl: A Case Report and Analysis.
Clavicular fractures are some of the most common bone injuries in the paediatric population, yet the rates of nonunion are very low under 18 years. To the best of our knowledge, posttraumatic nonunion of the clavicle in a paediatric population is rarely reported. We report the case of an 11-year-old girl who presented with a nondislocated fracture of the midshaft to the proximal third of the right clavicle. Initial conservative treatment by sling immobilization demonstrated radiologically confirmed healing at 3 months. However, at 1-year follow-up, she presented with painful nonunion. Diagnostic MRI and CT exams confirmed a pseudoarthrosis, requiring elective open reduction and internal fixation with the aid of an ipsilateral iliac crest bone graft.


Genetic typing of classical swine fever virus isolates from China.
The E2 genes of 73 classical swine fever virus (CSFV) originated from CSF suspected cases in different regions of China were genetically characterized and compared with reference CSF viruses. All Chinese viruses that characterized were segregated into two major groups and subdivided into four subgroups. Most of isolates (61.6%) belonged to group 2 and were further divided into three subgroups: subgroup 2.1, 2.2 and 2.3. Subgroup 2.1 was the largest subgroup which contained 46.6% of isolates, while subgroup 2.3 was the smallest subgroup which contained only one isolate (1.4%). The remaining 38.4% of isolates were classified into subgroup 1.1 within group 1. However, no group 3 and subgroups 1.2 and 1.3 viruses were found in this study. This study has provided epidemiological information useful for assessing the virus origin and establishing a national prevention and control strategy against the disease.


Cervical spine stenosis in chondrodysplasia punctata.
Chondrodysplasia punctata (CDP) is a rare skeletal dysplasia characterized by stippled epiphyses during infancy. The frequency is probably underdiagnosed because of the large heterogeneity in this group. Many genotypic variations exist. Although cervical instability is commonly seen in many skeletal dysplasias, cervical spine stenosis associated with CDP is very rare. We report a boy with phenotypic features of brachytelephalangic chondrodysplasia punctata (BCDP) who had severe cervical spine stenosis successfully corrected by vertebrectomies of C6 and C7 with a fibular strut graft. We discuss the significance of this association.


Pseudocyst of the auricle: a review of 21 cases.
Pseudocyst of the auricle (benign idiopathic cystic chondromalacia) is rare. Only 20 cases have been previously reported in the literature. Our study retrospectively reviews 21 additional cases. We conclude that idiopathic cystic chondromalacia can occur in both sexes, in all races, and at any age. The differential diagnoses for idiopathic cystic chondromalacia are relapsing polychondritis and chondrodermatitis nodularis chronica helicis. Recurrence of idiopathic cystic chondromalacia is uncommon following adequate local treatment.


Treatment of adenoviral keratoconjunctivitis with a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study.
To determine the efficacy of combination povidone-iodine (PVP-I) 1.0% eyedrops and dexamethasone 0.1% eyedrops in the treatment of adenoviral keratoconjunctivitis. In a prospective, randomized, controlled, double-blinded clinical trial patients with recent adenoviral keratoconjunctivitis (diagnosed clinically and confirmed by PCR), we randomly divided into three treatment groups: study group - received PVP-I 1.0% and dexamethasone 0.1%, control 1 group - received dexamethasone 0.1% and control 2 group - received lubricating eyedrops (hypromellose 0.3%). The treatment was administered four times a day in each group. All patients were examined and filled a questionnaire before treatment and on the 3rd, 5th and 7th days of treatment. We included in the study 78 eyes (26 in each group). Adenovirus type 8 was the most common pathogen (83% of cases). The fastest improvement in patients red eyes, discharge, superficial punctate keratitis and pseudomembranes was observed in the study group (p < 0.001). Those patients reached a near complete recovery in 5-7 days, which was also confirmed by reduction in Adenovirus titres by PCR. The slowest improvement was in the control 2 group. Subepithelial infiltrates (SEI) were observed in 44% of the control 1 group, 20% of the control 2 group and in 0% of the study group. The rate of reduction in Adenovirus titres was the slowest in the control 1 group. The combination of PVP-I 1.0% and dexamethasone 0.1% four times a day can reduce symptoms and expedite recovery in epidemic keratoconjunctivitis patients.


Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke.
Angiogenesis is a crucial defense response to hypoxia that regulates the process of raising the promise of long-term neurologic recovery during the management of stroke. A high expression of antiangiogenic factors leads to the loss of neovascularization capacity in pathologic conditions. We have previously documented an impairment of the cerebral vessel perfusion and neovascularization in the cortex neighboring the stroke-induced lesion, which was accompanied by an activation of semaphorin 3E (Sema3E)/PlexinD1 after ischemic stroke. In this study, we employed micro-optical sectioning tomography to fully investigate the details of the vascular pattern, including the capillaries. We found that after transient middle cerebral artery occlusion, inhibiting PlexinD1 signaling led to an organized recovery of the vascular network in the ischemic area. We then further explored the possible mechanisms. In vivo, Sema3E substantially decreased dynamic delta-like 4 (DLL4) expression. In cultured brain microvascular endothelial cells, Sema3E down-regulated DLL4 expression via inhibiting Ras-related C3 botulinum toxin substrate 1-induced JNK phosphorylation. At the microcosmic level, Sema3E/PlexinD1 signaling promoted F-actin disassembly and focal adhesion reduction by activating the small guanosine triphosphatase Ras homolog family member J by releasing RhoGEF Tuba from direct binding to PlexinD1, thus mediating endothelial cell motility and filopodia retraction. Our study reveals that Sema3E/PlexinD1 signaling, which suppressed endothelial DLL4 expression, cell motility, and filopodia formation, is expected to be a novel druggable target for angiogenesis during poststroke progression.-Zhou, Y.-F., Chen, A.-Q., Wu, J.-H., Mao, L., Xia, Y.-P., Jin, H.-J., He, Q.-W., Miao, Q. R., Yue, Z.-Y., Liu, X.-L., Huang, M., Li, Y.-N., Hu, B. Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke.


Induction of parasite-specific helper T lymphocytes during Trypanosoma cruzi infections in mice.
Development of parasite-specific T helper cells was examined in mice infected with Trypanosoma cruzi. At various times during the course of infection mice were challenged with TNP conjugated to fixed culture forms of T. cruzi (TNP-TC), and the resultant splenic plaque-forming cells (PFC) against TNP were determined. By day 10 post-infection significant responses against TNP-TC were observed but not against TNP-BSA. Infected mice that were not challenged with TNP-TC did not produce anti-TNP PFC, which demonstrated that the TNP-TC response was not the result of nonspecific B cell activation. Treatment of spleen cells from infected mice with anti-theta antiserum plus C ablated the anti-TNP-TC response when these cells were transferred to normal mice that were subsequently challenged with TNP-TC, whereas treatment of the cells with anti-Ig plus C prior to transfer had no effect on the TNP-TC response. These results demonstrate enhancement of parasite-specific Th activity of mice infected with T. cruzi and that cell-cell interaction in development of responses to neoantigens is fully functional when sensitized Th are present, even though the animals are unresponsive to heterologous antigens.


Morphological diversity of Quercus fossil pollen in the northern South China Sea during the last glacial maximum and its paleoclimatic implication.
We aimed to obtain high resolution vegetation data and climate information about the LGM in the inland of the northern SCS based on key pollen types. Dominant Quercus fossil pollen grains in the core from the continental shelf of the northern SCS have been identified at the infrageneric level by using scanning electron microscopy. Based on tectum ornamentation, we recognized five sculpture types of Quercus pollen, namely, rodlike, rodlike masked, rodlike vertical, verrucate and micro-verrucate. Such a high diversity of Quercus fossil pollen types indicated that broadleaved forests were widely distributed in the inland along the northern SCS and included species of the subgenera Cyclobalanopsis and Quercus, of which subgenus Cyclobalanopsis populations were highly dominant. Low abundance of deciduous Quercus pollen probably derived from temperate-subtropical forests, while abundant evergreen pollen types of subgenura Quercus and Cyclobalanopsis, as well as other pollen of broadleaved taxa in the pollen assemblages, strongly suggest that the inland has been covered by dense subtropical forests. Consequently, the warm and humid subtropical climate prevailed during the LGM in the inland along the northern SCS. Our results shed new light on regional climatic conditions during the LGM in eastern Asia based on high diversity of Quercus fossil pollen in marine deposits from northern SCS.


Differentiation of human bone marrow stromal cells into neural-like cells induced by sodium ferulate in vitro.
Human marrow stromal cells (hMSCs) are multipotential stem cells, capable of differentiating into bone, cartilage, fat and muscle. Several recent reports demonstrated that hMSCs have been also differentiated into neural cells. However, only a few reported inducers are applicable for clinical use. This work is to explore the effects of sodium ferulate (SF) on differentiation of hMSCs into neural cells in vitro. We found that hMSCs could be induced to the cells with typical neural morphology when cultured with SF. The cells express neural proteins, such as nestin, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP). About 30% of the hMSC-derived cells expressed nestin when cultured with SF for 3 h, but no expression was detected after 24 h. The percentages of positive cells for NSE or GFAP were about 67% and 39% separately at 6 h, and reached the plateau phage after treatment with SF for 3 days. The data suggest that SF can induce hMSCs to differentiate into neural-like cells in vitro.


Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE2) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2 produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.


Association of smoking and other risk factors with Fuchs' endothelial corneal dystrophy severity and corneal thickness.
We investigated effects of smoking and other risk factors on the development of advanced Fuchs' endothelial corneal dystrophy (FECD) and on central corneal thickness (CCT). Eyes from Caucasian probands, affected and unaffected family members, and unrelated controls matched for age from the FECD Genetics Multi-Center Study (n = 2044 subjects) were examined. Univariate and multivariate models, adjusted for family correlations, were used to determine the effect of smoking, sex, diabetes, and age on FECD case/control status and CCT. In a multivariate model, sex and smoking were associated significantly with advanced FECD (grades 4-6) development (P = 0.016 and P = 0.047, respectively). Female sex increased odds by 34%. Smoking increased odds by 30%. In a multivariate model, diabetes was associated with an increase of 9.1 μm in average CCT (P = 0.021). Female sex was associated significantly with a decrease in average CCT by 6.9 μm (P = 0.015). Smoking had no significant effect on CCT in any model. As shown previously, advanced FECD was associated with large increases in CCT (31.4-94.2 μm). Smoking was associated with an increased risk of advanced FECD and self-reported diabetes was associated with increased CCT. Further study of the impact of smoking and diabetes on FECD development and changes in corneal thickness is warranted.


A comparison of intra-operative cell-saving strategies upon immediate post-operative outcomes after CPB-assisted cardiac procedures.
Cardiotomy suction has been associated with adverse outcomes under routine conditions in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). We hypothesized that the routine use of a cell saver (CS) in place of the cardiotomy sucker would have no negative impact on transfusion rate (TR), chest tube drainage (CTD), ventilation time (VT) or intensive care unit length of stay (ICULOS) while avoiding the detrimental effects of cardiotomy suction. Retrospective data were collected from 69 patients where a cell saver was not used (NCS). Prospective data were collected from 219 patients who were followed after the implementation of an intra-operative cell saver. No significant increase in transfusion rate, chest tube drainage or ventilation time was found between the NCS group and the CS group. However, post-operative hemoglobin concentrations were significantly higher in the CS group (0.0001) and the CS group spent significantly less time in the ICU (p=0.018).


Tension production and thin-filament protein isoforms in developing rat myocardium.
The calcium sensitivity of tension production and the expression of troponin I (TnI) and troponin T (TnT) isoforms in skinned neonatal (7 days after birth) and adult rat myocardium were determined. Isometric tension was measured after activation at a known resting sarcomere length in ventricular trabeculae at adult and, for the first time, neonatal ages. Analysis of the tension-pCa relationships indicates a greater calcium sensitivity (approximately 0.3 pCa units) in neonatal ventricular trabeculae compared with adult trabeculae. The maximal isometric tension-generating ability (i.e., tension-tissue cross-sectional area) is threefold greater in adult compared with neonatal trabeculae. Developmental transitions in TnI and TnT isoform expression in atrial and ventricular tissue were examined simultaneously and were found to be dissimilar. Shifts in the expression of TnT isoforms precede shifts in TnI isoforms in ventricular tissue. The opposite pattern occurs in atrial tissue, with shifts in TnI preceding those in TnT. The results show that the greater calcium sensitivity of neonatal compared with adult rat ventricular tissue is associated with developmental changes in both TnT and TnI isoform expressions. These isoform expression patterns may facilitate myocardial tension production at the neonatal stage, when the tension-generating ability of individual trabeculae is much lower than that in the adult.


Subalpine conifers in different geographical locations host highly similar foliar bacterial endophyte communities.
Pines in the subalpine environment at Niwot Ridge, CO, have been found to host communities of acetic acid bacteria (AAB) within their needles. The significance and ubiquity of this pattern is not known, but recent evidence of nitrogen (N)-fixing activity in Pinus flexilis (limber pine) foliage calls for a better understanding of the processes that regulate endophytic communities in forest tree canopies. Here, to test if AAB dominate the foliar bacterial microbiota in other subalpine locations, we compared the 16S rRNA community in needles from P. flexilis and P. contorta (lodgepole pine) growing in the Eastern Sierra Nevada, CA, and Niwot Ridge, CO. AAB made up the majority of the bacterial community in both species at both sites. Multiple distinct AAB taxa, resolved at the single nucleotide level, were shared across host species and sites, with dominant OTUs identical or highly similar to database sequences from cold environments, including high altitude air sampled in Colorado, and the endosphere of Arctic plants. Our results suggest strong selection for community composition, potentially amplified by the long lifespan of individual Pinus needles, along with low dispersal constraints on canopy bacteria.


Recent advancements of covalent organic frameworks (COFs) as proton conductors under anhydrous conditions for fuel cell applications.
Recent electrochemical energy conversion devices require more advanced proton conductors for their broad applications, especially, proton exchange membrane fuel cell (PEMFC) construction. Covalent organic frameworks (COFs) are an emerging class of organic porous crystalline materials that are composed of organic linkers and connected by strong covalent bonds. The unique characteristics including well-ordered and tailorable pore channels, permanent porosity, high degree of crystallinity, excellent chemical and thermal stability, enable COFs to be the potential proton conductors in fuel cell devices. Generally, proton conduction of COFs is dependent on the amount of water (extent of humidity). So, the constructed fuel cells accompanied complex water management system which requires large radiators and airflow for their operation at around 80 °C to avoid overheating and efficiency roll-off. To overcome such limitations, heavy-duty fuel cells require robust proton exchange membranes with stable proton conduction at elevated temperatures. Thus, proton conducting COFs under anhydrous conditions are in high demand. This review summarizes the recent progress in emerging COFs that exhibit proton conduction under anhydrous conditions, which may be prospective candidates for solid electrolytes in fuel cells.


Bessel X waves in two- and three-dimensional bidispersive optical systems.
We show that new families of two- and three-dimensional nondiffracting Bessel X waves are possible in linear bidispersive optical systems. These X waves can be observed in both bulk and waveguide configurations as well as in photonic crystal lattices that simultaneously exhibit normal and anomalous dispersive-diffractive properties in different spatial or spatiotemporal coordinates.


Surgical outcomes of complicated cataract with pediatric trematode granulomatous uveitis.
To describe the clinical characteristics and surgical outcomes of complicated cataract with pediatric trematodal granulomatous uveitis (TGU). Patients of cataract with TGU in the membranous (inactive) stage underwent cataract surgery with intraocular lens (IOL) implantation. Preoperative history and ophthalmic examination were conducted for all cases, whereas Schimphlug imaging and corneal topography were done for some patients. Postoperative follow up was done on the 1st, 2nd, and 5th postoperative days after surgery. Then, it was done at least at one, three, and six months postoperatively. Intraoperative and postoperative complications and the methods of their management were reported. Twelve eyes of 12 male children were included in this study ranging from 8 to 16y. The mean best corrected Snellen visual acuity (BCVA) was significantly improved from 0.09±0.06 preoperatively to 0.37±0.11 at the final visit 6mo postoperatively (P<0.001). Schimphlug imaging and corneal topography showed flattening of the anterior surface of the inferior cornea. Intraoperative difficulties and complications included the poor dilatability of the drown down pupil, strong posterior synechia between the anterior lens capsule and the iris at the site of the inferior retrocorneal vascularized membrane and hyphema. All cases underwent primary hydrophobic IOL implantation. Surgery for this type of cataract is relatively safe and effective. It is associated with some specific difficulties and complications that should be considered during surgery and follow up.


[Evaluation of myocardial viability using perfusion cardiac SPECT. 201-thallium rest/redistribution, 201-thallium rest/reinjection and technetium 99m tetrofosmin rest/postnitrates].
It has been demonstrated that nitrate administration enhances the detection of myocardial viability in thallium-201 and technetium-99m sestamibi myocardial perfusion studies. The aim of this study was to assess the influence of nitrate administration on technetium-99m tetrofosmin myocardial uptake in patients with coronary artery disease and left ventricular dysfunction. Twenty eight patients with coronary artery disease, previous myocardial infarction and left ventricular ejection fraction < 40% underwent, within 48 hours, rest/postnitroglycerin (0.4 mg sublingually) technetium-99m tetrofosmin single photon emission tomography (SPET), comparing these results with that of thallium-201 rest/redistribution SPET in 13 patients (first group) and with that of thallium-201 rest/reinjection SPET in the other 15 patients (second group). Tomograms based on the 3 spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake > or = 50% of peak activity. The percentage of peak activity at rest or after nitrate administration of technetium-99m tetrofosmin correlated, with that of thallium-201, at rest and after redistribution or reinjection (r = 0.8; p < 0.001). On resting technetium-99m tetrofosmin studies 167 of the 420 segments that were analysed had < 50% of peak activity. 14.5% of these segments showed reversibility after nitrate administration, with an increase in 99mTc-tetrofosmin uptake from 45 +/- 5% to 55 +/- 4% of peak activity (p = 0.001), in the first group, and from 40 +/- 9% to 57 +/- 9% of peak activity (p = 0.003), in the second group. Overall agreement between rest/postnitroglycerin technetium-99m tetrofosmin SPET studies and rest/redistribution or rest/reinjection thallium-201 SPET studies, regarding the presence of myocardial viability, was 87% and 90%, respectively. All except one reversible segments on tetrofosmin studies after nitrates had viability criteria on thallium studies. Nitrate administration at rest enhances the detection of myocardial viability using technetium-99m tetrofosmin SPET, correlating with viability criteria observed on thallium studies. It represents a simple and useful technique in the assessment of myocardial viability.


Fatal visceral varicella-zoster developing early after autologous hematopoietic stem cell transplantation for refractory diffuse large B-cell lymphoma.
A middle-aged woman who had undergone autologous hematopoietic stem cell transplantation (HSCT) 1 month previously suffered severe epigastralgia and relapse of lymphoma. The epigastralgia was not relieved by chemotherapy. Thereafter, her pancreatic and hepatic enzyme levels were markedly elevated and disseminated varicella emerged. Despite acyclovir administration, her general condition deteriorated rapidly and she died. Serum varicella zoster virus (VZV) DNA level was shown to be elevated and a diagnosis of disseminated VZV infection was established postmortem. In patients with severe abdominal pain following HSCT, early suspicion and therapeutic intervention for VZV are important, even in the absence of skin lesions.


Bound and unextractable pesticidal plant residues: chemical characterization and consumer exposure.
Plants are well known to incorporate pesticides into bound and unextractable residues that resist solubilization in common laboratory solvents and are therefore not accessible to standard residue analysis. A characterization of such residues has been proposed for incorporation rates above trigger values of 0.05 mg kg(-1) parent pesticide equivalents, or percentage values of 10% (United States Environmental Protection Agency, 1995) or 25% (Commission of the European Communities, 1997) of the total radioactive residue. These trigger values are often exceeded. The present review describes the current status of the chemical characterization and animal bioavailability of bound and unextractable residues that may be xenobiotic in nature or result from natural recycling of simple degradation products. The latter case represents a mechanism of detoxification. Bound residues have been shown to be covalent or non-covalent in nature. With regard to the plant matrix molecules involved, incorporation into proteins, lignins, pectins, hemicelluloses and cutins has been demonstrated, and four covalent linkage types are known. Animal feeding experiments have revealed cases of low as well as high bioavailability. Many of the studies are limited by experimental uncertainties and by results only being reported as relative percentage values rather than absolute exposure. A preliminary value of absolute exposure from bound and unextractable residues is derived here for the first time from eight case studies. The mean exposure (ca 1.5 mg kg(-1) pesticidal equivalents) exceeds some of the existing maximum residue levels (MRLs) of residual free pesticides that are typically in the range of 0.05-1 mg kg(-1). A mathematical framework for the correction of current maximum residue levels is presented for cases of highly bioavailable bound residues. As bound pesticidal residues in food plants could represent a source of significant consumer exposure, an experimental test scheme is proposed here. It consists of basic chemical characterization, model digestibility tests and, in exceptional cases, animal bioavailability and additional toxicological studies.


The modern implementation of patient blood management (PBM) in Malaysia: the use of intravenous iron in severe anaemia with iron deficiency - A Case Report.
Anaemia is a common condition in Malaysia, and is mostly due to iron deficiency. In many cases, allogeneic blood transfusion (ABT) is administered unnecessarily to treat anaemia. Patient blood management (PBM) is a concept whereby a patient becomes his or her "own blood bank", instead of receiving ABT. The concept encompasses three pillars namely optimising erythropoiesis, minimising blood loss and harnessing human physiological reserve. We present a safe and fruitful outcome of managing severe anaemia without utilising any ABT, made possible with the PBM approach including administration of intravenous iron.


Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer (Dukes' class C): prolongation of disease-free interval and survival.
The poor postsurgical prognosis in patients with colorectal cancer of the Dukes' C classification has prompted a clinical trial of adjuvant immunotherapy versus chemoimmunotherapy intended to prolong either the disease-free interval or the overall survival or both. One hundred and twenty-one patients have been entered on this study. Fifty-two patients received BCG alone and 69 patients received the combination of 5-FU and BCG. The disease-free interval and the overall survival were compared with similar parameters in a group of historical controls with similar prognostic characteristics who were operated on in our institution prior to the initiation of the current study. There was no difference as yet between BCG alone and the combination of 5-FU + BCG in terms of both the disease-free interval and the survival. Both treatments, however, had significantly better results than the surgical controls. Adjuvant therapy, especially with BCG is advocated for patients with colorectal carcinoma, Dukes' C class, following potentially curative surgery.


Protective role of vitamin E preconditioning of human dermal fibroblasts against thermal stress in vitro.
Oxidative microenvironment of burnt skin restricts the outcome of cell based therapies of thermal skin injuries. The aim of this study was to precondition human dermal fibroblasts with an antioxidant such as vitamin E to improve their survival and therapeutic abilities in heat induced oxidative in vitro environment. Fibroblasts were treated with 100μM vitamin E for 24h at 37°C followed by heat shock for 10min at 51°C in fresh serum free medium. Preconditioning with vitamin E reduced cell injury as demonstrated by decreased expression of annexin-V, cytochrome p450 (CYP450) mediated oxidative reactions, senescence and release of lactate dehydrogenase (LDH) accomplished by down-regulated expression of pro-apoptotic BAX gene. Vitamin E preconditioned cells exhibited remarkable improvement in cell viability, release of paracrine factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), stromal derived factor-1alpha (SDF-1α) and also showed significantly up-regulated levels of PCNA, VEGF, BCL-XL, FGF7, FGF23, FLNβ and Col7α genes presumably through activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. The results suggest that pretreatment of fibroblasts with vitamin E prior to transplantation in burnt skin speeds up the wound healing process by improving the antioxidant scavenging responses in oxidative environment of transplanted burn wounds.


Smoking related cancers: a brief report on problem solving, distress, and risk behaviors in patients and caregivers.
Cancer diagnoses may adversely affect emotional functioning in patients and their caregivers, which in turn may increase risk behaviors, such as tobacco and alcohol use. This study investigates the relationships among problem-solving ability, distress, and risk behaviors in patients with head/neck and lung cancer and their caregivers. The authors hypothesized that patients and caregivers who experienced higher distress would engage in more risk behaviors, but that Social Problem-Solving (SPS) would moderate this effect, in that those who possessed greater SPS ability would engage in fewer risk behaviors. Twenty-one cancer patients and 11 of their caregivers were surveyed shortly after diagnosis. Participants completed the Profile of Mood States, the Social Problem-Solving Inventory-Revised, and measures of tobacco and alcohol use. Total SPS ability was higher in patients than caregivers but generally low in both groups. Total distress was lower in patients compared to caregivers. Mean comparisons indicated that caregivers smoked more cigarettes per day and consumed more alcohol than patients. Results indicate that patients and caregivers may have a decreased ability to solve problems, and that caregivers engage in more frequent risk behaviors than patients, suggesting that caregivers may be at risk and warrant further study. The study design prevents causative conclusions and limited sample size prohibits more complex analyses. Further research on social problem-solving ability, distress, and risk behaviors may reveal more robust relationships and provide insight for intervention development for these groups.


Exploring substrate scope and stereoselectivity of P450 peroxygenase OleTJE in olefin-forming oxidative decarboxylation.
As recently reported, the olefin-forming oxidative decarboxylation of straight-chain C4-C22 carboxylic acids catalyzed by P450 peroxygenase OleTJE constitutes a mild alkene synthesis. The present study shows that structurally different carboxylic acids are also accepted, including those that generate di-substituted olefins. Exploratory mutational experiments lead to increased trans-selectivity.


Food allergy in migraine. Study of dietary exclusion and RAST.
Two-thirds of severe migraineurs were allergic to certain foods, shown by dietary exclusion and subsequent challenge. Radioallergosorbent test confirmed the relevance of these foods. Oral sodium cromoglycate protected these patients from food challenges. The initial specific allergic reaction in the gut may result in increased mucosal permeability which allows food antigens, complexes, or mediators to be absorbed and cause symptoms.


Gastrointestinal complications of mycosis fungoides.
Mycosis fungoides (MF) is an uncommon T-cell lymphoma which characteristically involves the skin. Two patients with MF are described who developed fatal complications secondary to involvement of the gastrointestinal tract. One developed malabsorption due to small intestinal involvement; the other had a massive haemorrhage from an ulcerated nodule of tumour in the stomach. The potential for extracutaneous spread is discussed, and it is emphasized that bowel infiltration should be considered in any patient with MF who develops gastrointestinal symptoms or complications.


In vitro reendothelialization. Microfilament bundle reorganization in migrating porcine endothelial cells.
An experimentally induced wound made in a confluent monolayer culture of porcine thoracic aortic endothelial cells (ECs) was studied 22 hours after wounding using 7-nitrobenz-2-oxa-1,3-diazole (NBD) phallacidin and immunofluorescence microscopy to localize actin and myosin containing microfilament (MF) bundles. ECs extending from the wound edge back toward the confluent monolayer showed a specific change in cell shape and in MF bundle distribution and orientation, which correlated with the cell migration behavior observed using time-lapse cinemicrophotography. The migrating ECs in the first zone, the leading zone, were polygonal to partially elongated in shape, and contained distinct central MF bundles oriented both parallel and perpendicular to the wound edge. The second zone, the elongated zone, was characterized by elongated cells with central MF bundles oriented parallel to the direction of migration. A third zone, the transitional zone, showed nonmigrating polygonal ECs containing prominent central and dense peripheral bands (DPB) of MF bundles. The central MF bundles were oriented randomly with respect to the wound edge. The MF bundles of the confluent resting monolayer were both centrally and peripherally located with the latter being more prominent. The results indicate that the reorientation of central MF bundles and reduction in the peripheral MF bundles are probably important in the reorganization of the cytoskeletal system during the conversion of stationary cells to migrating cells.


Burnout and Associated Risk Factors in Pediatric Residents.
Background: Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a low sense of personal accomplishment. The aim of this study was to identify burnout incidence in pediatric residents and evaluate possible risk factors for burnout. Methods: Using a cross-sectional study design, we approached all pediatric residents in the Saudi Pediatrics Residency Program in Riyadh, Saudi Arabia (n=457) between January and March 2019. The Maslach Burnout Inventory-Human Services Survey was used to assess burnout incidence. In addition, demographic factors, schedule burden, career choice satisfaction, and work-life balance were assessed. Results: The response rate was 57.8% (264/457). Males represented 46.6%. Only 14% of the residents in the study were satisfied with their work-life balance, and 62% were satisfied with their career choice of pediatrics. The overall high burnout incidence was 15.9%, the high emotional exhaustion incidence was 63.6%, the high depersonalization incidence was 27.7%, and the low sense of personal accomplishment incidence was 48.5%. In the multivariate analysis, an increase in the average number of on-calls per month (odds ratio [OR]=1.66, 95% CI 1.12-2.46; P=0.012) and satisfaction with salary (OR=0.47, 95% CI 0.33-0.66; P<0.001) showed significant associations with high overall burnout. Conclusion: We found a high level of emotional exhaustion and a low sense of personal accomplishment among respondents. However, less than one-third of residents had feelings of depersonalization or overall high burnout. Residency program directors may need to make modifications in their programs to ensure a good work-life balance for residents that will help ensure that these physicians provide safe and sustained patient care.


Clinical response to etodolac in the management of pain.
Etodolac is a new nonsteroidal anti-inflammatory drug (NSAID). Published and unpublished data on etodolac in pain management are reviewed to assess the analgesic effectiveness of this drug. Data are presented from four representative studies that showed the analgesic activity of etodolac in postsurgical pain models. These results suggest that the drug would have analgesic utility in other painful conditions such as gout and musculoskeletal disorders. The efficacy of etodolac in such conditions is confirmed by the results from eight controlled clinical studies in patients with gouty arthritis, tendinitis and bursitis, and acute sports injuries. Etodolac 200 or 300 mg twice a day (b.i.d.) or 200 mg three times a day (t.i.d.) was compared with naproxen 500 mg b.i.d. and diclofenac 50 mg b.i.d. or 50 mg t.i.d. All three NSAIDs provided analgesia, and etodolac was comparable in efficacy to the comparators. The data presented in this review suggest a future role for etodolac as an analgesic as well as an anti-inflammatory agent.


Protection against cognitive impairment and modification of epileptogenesis with curcumin in a post-status epilepticus model of temporal lobe epilepsy.
Epileptogenesis is a dynamic process initiated by insults to the brain that is characterized by progressive functional and structural alterations in certain cerebral regions, leading to the appearance of spontaneous recurrent seizures. Within the duration of the trauma to the brain and the appearance of spontaneous recurrent seizures, there is typically a latent period, which may offer a therapeutic window for preventing the emergence of epilepsy. Previous animal studies have shown that curcumin can attenuate acute seizure severity and brain oxidative stress, but the effect of curcumin on epileptogenesis has not been studied. We examined the effect of continued administration of curcumin during the latent period on epileptogenesis and the deleterious consequences of status epilepticus in adult rats in a post-status epilepticus model of temporal lobe epilepsy induced by kainic acid. We demonstrate that, while administration of curcumin treatment during the latent period does not prevent occurrence of spontaneous recurrent seizures after status epilepticus, it can attenuate the severity of spontaneous recurrent seizures and protect against cognitive impairment. Thus, treatment with curcumin during the latent period following status epilepticus is beneficial in modifying epileptogenesis.


Spread of an enteric 'marker' organism during evisceration of New York dressed poultry in a simulated kitchen environment.
1. Five volunteers, with experience of eviscerating poultry or game birds in the home, each eviscerated three New York dressed chicken carcases that had been artificially inoculated in the colon with a readily identifiable "marker' strain of Escherichia coli. 2. In all cases, evisceration resulted in breakage of the intestines at one or more sites, often with leakage of gut contents, or extrusion of faeces from the cloaca because of pressure on the colon during the manipulations involved. 3. The marker organism was detected in the vent region and abdominal cavity of each carcase and sometimes on the breast and back, which appeared to reflect the degree of handling during evisceration, because the hands of each individual became heavily contaminated. 4. With some individuals, the marker also spread beyond the immediate preparation area and was detected on exposure plates. 5. Results support the view that evisceration of poultry in a domestic environment could lead to cross-contamination of other foods with any food-borne human pathogens present.


Lung function of children treated for malignant extrapulmonary tumors.
Lung function was studied in 29 children suffering from extrapulmonary tumors of varying etiology (Wilm's tumor, n = 7; bone malignancy, n = 17; nasopharyngeal epithelioma, n = 5). Lung volume: vital capacity (VC) and functional residual capacity (FRC), lung mechanics: lung resistance (RL), dynamic lung compliance (CLdyn) and static lung compliance (CLstat) and lung transfer factor for CO (TLCO), and blood gases were determined at different stages of therapy: at t0, before any aggressive treatment for respiratory function; at t1, after the initiation of polychemotherapy with or without local tumoral treatment (surgery or local irradiation); at t2, less than 6 months after onset of thoracopulmonary irradiation (whole lung irradiation at 20 grays) (group I), or local thoracopulmonary irradiation at high exposure greater than 40 grays (group II); at t3 after more than 6 months following irradiation with chemotherapy maintained; at t4, after cessation of all treatment (mean: 25 months +/- 14 after cessation of treatment). At t0, lung function data in children without pulmonary metastases did not deviate from predicted values. At t1, group I showed a significant decrease in CLdyn, which could be due to chemotherapy and for 5 children to consequences of abdominal surgery. In group II, only two children had a low CLdyn and also a significant decrease in VC (possibly due to the site of the tumor). After irradiation (at t2), FRC, TLCO and CLdyn were significantly lower than the predicted values and lower than at t1 in both groups (p greater than 0.01). At t3, functional parameters did not show any change compared to t2. At t4, FRC and TLCO were within normal limits in both groups but CLdyn, CLstat and the CLdyn/FRC ratio remained significantly decreased. It is suggested that these functional abnormalities are due to inadequate alveolar growth.


Low frequency acoustic method to measure the complex bulk modulus of porous materials.
In this work, an acoustic lumped element technique has been developed to measure the dynamic bulk modulus of porous materials in the low frequency range ( f<500 Hz). Based on the electroacoustic analogy of wave propagation inside a porous medium, an analytical derivation of the measurement method is given. Unlike other techniques, it requires the use of only two microphones placed in the cavity containing the sample being tested and in the loudspeaker box. The proposed method provides reliable results when the longitudinal viscous impedance within the medium is negligible with respect to the transversal thermal impedance. The upper limit of the frequency validity range can be determined from the relationship absk̃d≈0.5, where k̃ is the acoustic wavenumber of the porous material and d is the sample thickness. Furthermore, some practical aspects related to the measure are also reported. To validate the methodology, experimental campaigns have been performed on different typologies of materials (fibrous, uniform cross-section geometries, additive manufactured sample, and foam) in two laboratories. The experimental results show good agreement with the theoretical results within the frequency validity range.


General method for the synthesis of phenyliodonium ylides from malonate esters: easy access to 1,1-cyclopropane diesters.
A general method to access phenyliodonium ylides from malonates has been developed. These ylides provide easy access to a variety of useful 1,1-cyclopropane diesters using rhodium or copper catalysis. Moreover, the iodonium ylide of dimethyl malonate was obtained in 78% yield using improved conditions that involve a simple filtration step to isolate the desired product. This ylide was shown to be a safer and convenient alternative to the corresponding diazo compound and a very efficient way to 1,1-cyclopropane diesters when used with a catalytic amount of Rh(2)(esp)(2).


Role of poly(ADP-ribosyl)ation during human spermatogenesis.
Genomic stability of cells is known to be linked to their poly(ADP-ribosyl)ation capacity. We aimed to demonstrate, for the first time, the patterns of poly(ADP-ribosyl)ation during human spermatogenesis. Retrospective case-control study. Teaching hospital. Azoospermic men who underwent testicular biopsy for sperm recovery. Testicular biopsy evaluation by immunohistochemistry for the expression of poly(ADP-ribose) polymerase-1 (PARP-1) enzyme and of poly(ADP-ribose) (PAR) (an indicator for PARP activity.) The subcellular localization of both markers in testes with full spermatogenesis (obstructive azoospermia), spermatocyte maturation arrest, or Sertoli cell-only syndrome. Expression of both markers was localized in germ cell nuclei in full spermatogenesis: PAR expression, indicating PARP activity, was exhibited in round and elongating spermatids and in a subpopulation of primary spermatocytes. Strong immunoreactivity for PAR was identified in all of the spermatocytes in maturation arrest at the spermatocyte level. Sertoli cells lacked immunoreactivity for both markers, whereas other somatic testicular cells were rarely immunostained. The detection of PAR expression in germ-line cells and its subcellular localization in meiotic and postmeiotic prophases demonstrates chromatin modifications occurring during spermatogenesis and establishes a key role for poly(ADP-ribosyl)ation in germ cell differentiation, presumably to safeguard DNA integrity.


Polymer models with optimal good-solvent behavior.
We consider three different continuum polymer models, which all depend on a tunable parameter r that determines the strength of the excluded-volume interactions. In the first model, chains are obtained by concatenating hard spherocylinders of height b and diameter rb (we call them thick self-avoiding chains). The other two models are generalizations of the tangent hard-sphere and of the Kremer-Grest models. We show that for a specific value [Formula: see text], all models show optimal behavior: asymptotic long-chain behavior is observed for relatively short chains. For [Formula: see text], instead, the behavior can be parametrized by using the two-parameter model, which also describes the thermal crossover close to the θ point. The bonds of the thick self-avoiding chains cannot cross each other, and therefore the model is suited for the investigation of topological properties and for dynamical studies. Such a model also provides a coarse-grained description of double-stranded DNA, so that we can use our results to discuss under which conditions DNA can be considered as a model good-solvent polymer.


Priming of CD8(+) T Cell Responses to Liver Stage Malaria Parasite Antigens.
While the role of malaria parasite-specific memory CD8(+) T cells in the control of exo-erythrocytic stages of malaria infection is well documented and generally accepted, a debate is still ongoing regarding both the identity of the anatomic site where the activation of naive pathogen-specific T cells is taking place and contribution of different antigen-presenting cells (APCs) into this process. Whereas some studies infer a role of professional APCs present in the lymph nodes draining the site of parasite injection by the mosquito, others argue in favor of the liver as a primary organ and hepatocytes as stimulators of naïve parasite-specific T cell responses. This review aims to critically analyze the current knowledge and outline new lines of research necessary to understand the induction of protective cellular immunity against the malaria parasite.


High pressure phase transitions in the rare earth metal erbium to 151 GPa.
High pressure x-ray diffraction studies have been performed on the heavy rare earth metal erbium (Er) in a diamond anvil cell at room temperature to a pressure of 151 GPa and Er has been compressed to 40% of its initial volume. The rare earth crystal structure sequence hcp → Sm type → dhcp → distorted fcc (hcp: hexagonal close packed; fcc: face centered cubic; dhcp: double hcp) is observed in Er below 58 GPa. We have carried out Rietveld refinement of crystal structures in the pressure range between 58 GPa and 151 GPa. We have examined various crystal structures that have been proposed for the distorted fcc (dfcc) phase and the post-dfcc phase in rare earth metals. We find that the hexagonal hR 24 structure is the best fit between 58 and 118 GPa. Above 118 GPa, a structural transformation from hR 24 phase to a monoclinic C 2/m phase is observed with a volume change of - 1.9%. We have also established a clear trend for the pressure at which a post-dfcc phase is formed in rare earth metals and show that there is a monotonic increase in this pressure with the filling of 4f shell.


RNA polymerase holoenzymes can share a single transcription start site for the Pm promoter. Critical nucleotides in the -7 to -18 region are needed to select between RNA polymerase with sigma38 or sigma32.
The Pm promoter of the benzoate meta-cleavage pathway is transcribed with E sigma32 or E sigma38 according to the growth phase, with an identical transcriptional start site. To investigate sequence determinants in the interaction between either of the two RNA polymerases and Pm, all possible single mutants between positions -7 and -18 were generated, and the activity in the exponential and stationary phases of the resulting mutant promoters was compared. The results precisely delimited a -10 element between positions -7 and -12 (TAGGCT), which defined a promoter sharing nucleotides with both sigma38 and sigma32 consensus. The first two and the last positions of this hexamer were crucial for recognition by both polymerases. Position -10 was the only one specifically recognized by E sigma38, whereas positions -8, -9, and the C-track between positions -14 and -17 were important for specific E sigma32 recognition. Western blots showed that sigma32 was only detectable in the exponential phase, and sigma38 appeared in the early stationary phase. In the rpoH mutant KY1429, sigma38 was already present in the exponential growth phase both free and bound to the RNA polymerase core, in good correlation with the transcription levels found. Pm seems to be optimized for recognition by sigma32 as an initial response to the addition of effector to the medium and allows binding of the adaptable sigma38-dependent RNA polymerase in the stationary phase. XylS is always required for Pm transcription. Therefore, the mechanism that controls Pm expression involves specific nucleotide sequences, the abundance of free and core-bound sigma32 and sigma38 factors during growth, and the presence of the regulator activated by an effector.


CD61, CD31, and CD34 improve diagnostic accuracy in gastric antral vascular ectasia and portal hypertensive gastropathy: An immunohistochemical and digital morphometric study.
Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are unusual but important causes of gastrointestinal bleeding with characteristic endoscopic appearances and critically different therapies. However, overlapping features and poor endoscopic-histologic correlation make their distinction challenging. We sought to determine whether CD31, CD34 (vascular markers), and CD61 (platelet marker) could aid in their differentiation. Cases included 11 antral specimens with histologic diagnoses of GAVE, 11 histologically diagnosed as PHG, and biopsies of GAVE (15) or PHG (12) suspected on endoscopy but without histologic agreement. Controls consisted of endoscopically and histologically normal antrum. Image analysis of CD31 and CD34-stained sections was performed to determine mucosal microvessel density (MVD). CD61 revealed thrombi in 100% of histologically confirmed cases of GAVE and 60% of cases suspected of GAVE on endoscopy alone; control biopsies were negative. CD61 was also positive in 26% of cases originally signed out as PHG. Review of hematoxylin and eosin slides from these CD61-positive PHG cases showed other features allowing their correct reclassification as GAVE. MVD was significantly higher in GAVE than PHG. MVD in histologically confirmed PHG did not differ significantly from endoscopically suspected PHG. Review of hematoxylin and eosin slides from the latter showed active gastritis obscuring recognition of ectatic vessels. In conclusion, CD61 reliably differentiates GAVE from PHG. MVD analysis can also assist in their distinction. In PHG, the increased vascularity may be subtle in an inflammatory background; vascular markers may serve as adjunct markers for identifying the aberrant vessels.


Effects of prenatal docosahexaenoic acid supplementation on offspring cardiometabolic health at 11 years differs by maternal single nucleotide polymorphism rs174602: follow-up of a randomized controlled trial in Mexico.
There is limited evidence regarding long-term effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring cardiometabolic health (CMH). Inconsistent results may be attributable to variants of fatty acid desaturase (FADS) genes. We aimed to evaluate the effect of prenatal DHA supplementation on offspring CMH and investigate effect modification by maternal FADS2 single nucleotide polymorphism (SNP) rs174602. We used follow-up data from a double-blind, randomized controlled trial in Mexico in which pregnant females received 400 mg/d of algal DHA or placebo from midgestation until delivery. The study sample included 314 offspring with data at age 11 y and maternal FADS genetic data (DHA: n = 160; Placebo: n = 154). We derived a Metabolic Syndrome (MetS) score from body mass index, HDL, triglycerides, fasting glucose concentrations, and systolic blood pressure. Generalized linear models were used to evaluate the effect of the intervention on offspring MetS score and test interactions between treatment group and genotype, adjusting for maternal, offspring, and household factors. Offspring MetS score did not differ significantly by treatment group. We observed evidence of effect modification by maternal SNP rs174602 (P = 0.001); offspring of maternal TT genotype who received DHA had lower MetS score relative to the placebo group (DHA (mean ± standard error of the mean (SEM)): -0.21 ± 0.11, n = 21; Placebo: 0.05 ± 0.11, n = 23; Δ= -0.26 (95% CI: -0.55, 0.04), P = 0.09); among CC maternal genotype carriers, offspring of mothers who received DHA had higher MetS score (0.18 ± 0.06, n = 62) relative to the placebo group (-0.05 ± 0.06, n = 65, Δ=0.24 (0.06, 0.41), P < 0.01). The effect of prenatal DHA supplementation on offspring MetS score differed by maternal FADS SNP rs174602. These findings further support incorporating genetic analysis of FADS polymorphisms in DHA supplementation trials. This trial was registered at clinicaltrials.gov as NCT00646360.


POPULATION STRUCTURE OF A CLONAL GORGONIAN CORAL: THE INTERPLAY BETWEEN CLONAL REPRODUCTION AND DISTURBANCE.
Clonality is a common feature of plants and benthic marine organisms. In some cases clonal propagation results in a modest increase in population density, while in other cases dense populations may be generated by the propagation of only a few clones. We analyzed the population structure of the clonal gorgonian Plexaura kuna across several reef habitats with a range of disturbance regimes in the San Blas Islands, Panama, and the Florida Keys, U.S.A. Using multilocus DNA fingerprinting to distinguish clones, we estimated that clones ranged in size from single individuals to 500 colonies. The number of genotypes identified on nine reefs ranged from three to 25. Population density and clonal structure varied markedly among reefs with GO :GE ranging from 0.03 to 1.00. On some reefs vegetative reproduction transformed P. kuna from a rare species to the numerically most abundant gorgonian. The effect of clonal propagation on P. kuna population structure was dependent on interactions between fragmentation and the reef environment (disturbance regime, substratum). We present a generalized model relating population structure of clonal species to disturbance and the mode of vegetative propagation. Disturbance promotes colony propagation and skews the size-frequency distribution of clones among P. kuna and many species that propagate via fragmentation. Propagation of these species is promoted by disturbance (disturbance sensitive), and they tend to have clones that are dispersed across local sites. Species that fragment and have dispersed clones, have high genotypic diversity in habitats with low levels of disturbance. Genotypic diversity then decreases at intermediate disturbance and increases again at the highest disturbance levels. Clonal species that do not rely on disturbance for vegetative propagation (disturbance insensitive) generally do not disperse and form aggregated clones. Among these taxa disturbance has a greater affect on individual survival than on propagation. Genotypic diversity is directly related to the level of disturbance until very high levels of disturbance, at which time genotypic diversity declines.


Effects of organic Ca antagonist, diltiazem, on neuromuscular transmission.
The effects of the organic "Ca antagonist" diltiazem on the frog neuromuscular junction was investigated. The addition of diltiazem to the bath solution increased the frequency of spontaneous miniature endplate potentials (MEPPs) and quantal content. The amplitude of the endplate current (EPC) recorded from a d-tubocurarine-blocked endplate was significantly decreased by diltiazem (20-200 microM). However, the amplitude of miniature endplate current (MEPC) was relatively unchanged by diltiazem. The same degree of decrease in the decay time constant was observed in both EPC and MEPC. ACh potentials induced by repetitive iontophoresis were depressed gradually by low concentrations of diltiazem (2, 5 microM), suggesting enhanced desensitization. Using a patch-clamp method, the effects of diltiazem on ACh-activated single current in chick cultured myotubes were examined. The addition of diltiazem to the bath solution shortened the mean open time in a dose-dependent manner between 10 and 50 microM. The voltage-dependence of mean open time disappeared in the presence of diltiazem, with little change in the channel conductance. The present experiments suggest that diltiazem acts on the ACh-activated channel as an open channel blocker.


Wet Sunscreens in the Gas Phase: Structures of Isolated and Microsolvated Oxybenzone.
New insights into the structural intricacies of solvated sunscreen compounds are presented. Using high-resolution rotational spectroscopy with supersonic jets and quantum-chemistry calculations, we navigate the conformational space of oxybenzone and oxybenzone-water clusters. We unambiguously assign the global minimum structure, resolving any prevailing ambiguities, and locate the primary hydration sites of the ground-state enol conformer. Two microsolvated molecular models of oxybenzone are validated by rotational spectroscopy of isotopically enriched species. Theoretical predictions based on these models suggest that water influences the ground-state enol-keto energetic constraints and that its effect is biased depending on which water docking-site is at play.


L-Arginine alleviates the testosterone reduction in heat-treated mice by upregulating LH secretion, the testicular antioxidant system and expression of steroidogenesis-related genes.
High temperature can reduce testes function, leading to decreased testosterone secretion. Dietary l-arginine (l-Arg) supplementation improves the semen quality and libido of boars. The present study investigated whether l-Arg could enhance the production of testosterone in mice exposed to high ambient temperature. Twenty-four 6-week-old male ICR mice were randomly divided into three groups: a control group, a heat-treated (HT) group and a group subjected to heat treatment plus 2mg kg-1 l-Arg (HT+Arg). l-Arg was administered to mice by oral gavage for 18 consecutive days, after which the HT and HT+Arg groups were placed into an incubator at 40°C for 30min every day for 5 days. Serum testosterone and LH concentrations were significantly increased in the HT+Arg compared with HT group, as was catalase, total superoxide dismutase and glutathione peroxidase activity and the expression of steroidogenesis-related genes steroidogenic acute regulatory protein (Star), steroidogenic factor-1 (Sf1), 17β-hydroxysteroid dehydrogenase 3 (Hsd17b3) and 17α-hydroxylase/17,20-lyase (Cyp17a1) in the testes. These results demonstrate that l-Arg can alleviate testosterone reductions in heat-treated mice by upregulating LH secretion, enhancing the antioxidant system and increasing the expression of testosterone synthesis-related genes.


[Evaluation of vaccine potency against viral hepatitis B performed with HB-vax II vaccine in a group with an increased risk for hepatitis B].
The aim of this investigation was to established the rate of seroconversion against hepatitis B after vaccination of workers of the National Institute of Cardiology who are at increased risk. All participants were HBs-Ag, and anti-HBs negative and also had normal standard hepatic laboratory tests. Vaccination was carried out according to following scheme: the first vaccination at t = 0, the second after one month and the third after six months. Vaccine was given intramuscular. The success of vaccination was monitored by the quantitative determination of antibodies against HBs-Ag (Anti-HBs) by the ELISA method (Abbott). After each vaccination, anti-HBs formation above 10 iu/l protective level was observed in 40.7%, 85.9%, and 97.1% of immunocompetent subjects after first, second, and third vaccination respectively. The acquired anti-HBs titer varies from individual to individual but in immunocompetent subjects the level of antibodies against HBs after third vaccination was 170 fold higher then those after first vaccination. These results seems to suggest that vaccine HB-Vax-II is effective and may by recommended in pre-exposure prophylaxis against hepatitis B.


Comparison of alternative remediation technologies for recycled gravel contaminated with heavy metals.
To evaluate the effects of different remediation methods on heavy metals contaminated recycled gravel, three immobilization agents (monopotassium phosphate, lime, nano-iron) and two mobilization agents (glyphosate, humic acid (HA)) were studied and compared. Results indicated that nano-iron powder was found to be more effective to immobilize Zn, Cu, Pb and Cd. Meanwhile, glyphosate presents a higher mobilization effect than HA with removal rates of about 66.7% for Cd, more than 80% for Cr, Cu and Zn, and the highest removal percentage of 85.9% for Cr. After the mobilization by glyphosate, the leaching rates of Zn, Cu and Cr were about 0.8%, and below 0.2% for Pb and Cd. The leaching rates after nano-iron powder treatment were 1.18% for Zn, 0.96% for Cr, 0.61% for Cu, 0.45% for Pb and Cd not detected. The formation and disappearance of metal (Zn/Cu/Cr/Pb/Cd) compounds were firmly confirmed through X-ray diffraction and scanning electron microscopy analyses on crystalline phases and morphological surface structures.


Previous corticosteroid exposure associates with an increased Pneumocystis jirovecii pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study.
HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality. We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality. We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis (n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis. 1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p < 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p < 0.001) or prednisone (49% versus 29%, p < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5-9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0-10.4, p < 0.0001) among HIV-negative patients with previous corticosteroid exposure. Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.


Hydroxyethylene sulfones as a new scaffold to address aspartic proteases: design, synthesis, and structural characterization.
Hydroxyethylene sulfones were developed as novel scaffolds against aspartyl proteases. A diastereoselective synthesis has been established to introduce the required side chain decoration with desired stereochemistry. Depending on the substitution of the hydroxyethylene sulfone core, micro- to submicromolar inhibition of HIV-1 protease is achieved for the S-configuration at P1 and R-configuration at the hydroxy-group-bearing backbone atom. This stereochemical preference is consistent with the S,R configuration of amprenavir. The racemic mixture of the most potent derivative (K(i) = 80 nM) was separated by chiral HPLC, revealing the S,R,S-enantiomer to be more active (K(i) = 45 nM). Docking studies suggested this isomer as the more active one. The subsequently determined crystal structure with HIV-1 protease, cocrystallized from a racemic mixture, exclusively reveals the S,R,S-enantiomer accommodated to the binding pocket. The transition state mimicking hydroxy group of the inhibitor is centered between both catalytic aspartates, while either its carbonyl or sulfonyl group forms H-bonds to the structurally conserved water mediating interactions between ligand and Ile50NH/Ile50NH' of both flaps. Biological testing of the stereoisomeric hydroxyethylene sulfones against cathepsin D and beta-secretase did not reveal significant inhibition. Most likely, the latter proteases require inverted configuration at the hydroxy group.


Suprasellar and intrasellar paragangliomas.
Neoplasms of the sellar region are entities with a large differential diagnosis. Although paraganglionic cells have not been demonstrated in the pituitary or adjacent structures, the existence of sellar region paragangliomas is well-documented. To elucidate, in this area the nature of these unusual tumors is relatively difficult. Clinical history, physical examination, radiographic investigation as well as intraoperative gross observation are the same as those of sellar meningioma or pituitary adenoma. Immunohistochemistry, using neuroendocrine markers and electron microscopy are the two definitive diagnostic methods to differentiate among these entities. The clinical management, the possible pathogenesis of the tumor, the importance of immunohistochemistry in making the diagnosis and the clinical outcome of these patients are discussed.


Blood transfusions, HIV and legal liability in South Africa.
This article deals with the legislation, regulations and clinical guidelines regulating blood transfusions in South Africa. Although these are aimed at protecting both the recipients and donors of blood, the risk of HIV infected blood being donated and transfused is on the increase, due to inter alia, the high prevalence of HIV infection among the South African population. The article discusses, in the absence of strict liability in South Africa, the possible legal liability of blood services, medical practitioners, the Department of Health, and the blood donor when a recipient of blood is infected. The need for informed consent by both the recipient and the donor is also discussed, as well as the legal repercussions where informed consent is lacking.


The Effect of Inhaled Corticosteroid Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study. A Randomized, Double-Blind, Multicenter Clinical Trial.
Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.Methods: Exacerbations and change from baseline in trough FEV1 and St. George's Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days.Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P < 0.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P = 0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce the annual on-treatment moderate/severe exacerbation rate (19%; P < 0.001) compared with UMEC/VI. The benefit of FF/UMEC/VI compared with UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P < 0.001; non-ICS users, 35% reduction; P = 0.018), and overall when excluding the first 30 days (29%; P < 0.001). Improvements from baseline with FF/UMEC/VI compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St. George's Respiratory Questionnaire, regardless of prior ICS use.Conclusions: These data support the important treatment effects of FF/UMEC/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.Clinical trial registered with www.clinicaltrials.gov (NCT02164513).


Spectrum of bleeding in acquired factor V inhibitor: a summary of 33 cases.
Coagulation factor V (FV) is an essential component of the prothrombinase complex, which activates the zymogen prothrombin to thrombin. Acquired FV inhibitor is rare and clinical symptoms are quite variable. The aim of this study was to summarize the spectrum of the bleeding presentation of acquired FV deficiency and characterize the underlying causes of the clinical symptoms. This study was designed as a descriptive retrospective and 30 case reports were included for further analysis. At least 33 cases of acquired FV inhibitor were investigated. Most patients have a presentation of bleeding and most of those are from hematuria and bleeding at surgical sites. Seven cases of asymptomatic acquired FV inhibitor were also detected. A total of 39.4% (19 of 33) of those cases with acquired FV inhibitor have an unknown cause. For those with known etiologies, chemical and drug-induced causes are the most common (30.8%).


Crown-root fracture of lower molar--restorative procedures.
Endodontically treated teeth may undergo crown, crown-root, or root fractures. The treatment of fractured teeth can be complicated, sometimes because of difficulties with the final restoration. This case report describes a case of crown-root fracture of a left lower first molar in which endodontic treatment and rapid orthodontic eruption of the tooth made a good prosthetic restoration possible.


Beneficial effects of N-acetylcysteine on hepatic oxidative stress in streptozotocin-induced diabetic rats.
Diabetes is one of the leading diseases worldwide and, thus, finding new therapeutic alternatives is essential. The development of non-alcoholic fatty liver disease is a notable diabetic complication. Therefore, antioxidant therapy became a leading topic in the world of diabetes research. The objective of this present study was to evaluate the effects of antioxidant N-acetylcysteine (NAC) administration on serum biochemical parameters and oxidative stress parameters in hepatic tissue of the diabetic rats. Thirty-two animals were divided in 4 groups (n = 8): G1, normal rats; G2, normal rats + NAC; G3, diabetic rats; and G4, diabetic rats + NAC. Diabetes was induced in diabetic groups through streptozotocin. NAC administration was effective in improving hyperglycemia and hypoinsulinemia, as well as reducing serum alanine-aminotransferase and urea, hepatic triglycerides accumulation, and oxidative stress biomarkers in the diabetic liver, as well as improving the activity of hepatic antioxidant enzymes. This effect was likely due to NAC's ability of restoring intracellular glutathione, an important compound for the antioxidant defense, as well as due to NAC's direct antioxidant properties. Thus, NAC administration was useful for reducing hepatic oxidative stress and decreased the deposit of triacylglycerols, minimizing diabetic hepatic damage, making it a promising therapeutic adjuvant in the future.


Analytic energy gradient of projected Hartree-Fock within projection after variation.
We develop a geometrical optimization technique for the projection-after-variation (PAV) scheme of the recently refined projected Hartree-Fock (PHF) as a fast alternative to the variation-after-projection (VAP) approach for optimizing the structures of molecules/clusters in symmetry-adapted electronic states at the mean-field computational cost. PHF handles the nondynamic correlation effects by restoring the symmetry of a broken-symmetry single reference wavefunction and moreover enables a black-box treatment of orbital selections. Using HF orbitals instead of PHF orbitals, our approach saves the computational cost for the orbital optimization, avoiding the convergence problem that sometimes emerges in the VAP scheme. We show that PAV-PHF provides geometries comparable to those of the complete active space self-consistent field and VAP-PHF for the tested systems, namely, CH2, O3, and the [Cu2O2]2+ core, where nondynamic correlation is abundant. The proposed approach is useful for large systems mainly dominated by nondynamic correlation to find stable structures in many symmetry-adapted states.


A rare complement component C4 restriction fragment length polymorphism in two families with systemic lupus erythematosus.
C4 null alleles with or without C4A,21-OHA gene deletions are associated with systemic lupus erythematosus (SLE) in various populations. We describe a new, rare C4 restriction fragment length polymorphism (RFLP), a Taq I 3.5 kb fragment, in 2 patients with SLE and their families. This RFLP is not associated with one particular major histocompatibility complex (MHC) haplotype and has not been reported in patients with SLE, patients with congenital adrenal insufficiency, or in healthy individuals.


In vitro propagation of Theileria annulata infected schizonts in different media supplemented with heterologous sera.
Efficacy of medium RPMI-1640 (supplied by Gibco USA, Centron and Hi-media) supplemented with horse, donkey, sheep and goat sera was evaluated for in vitro propagation of Theileria annulata (Hisar) infected bovine mononuclear cells. The results were compared with the growth rate in RPMI-1640 supplemented with foetal bovine serum (Gibco). RPMI-1640 (Gibco) proved to be the best medium for in vitro cultivation of the parasite infected cells. Foetal bovine serum could be easily, safely and reliably substituted with goat and sheep sera in the growth medium. Horse and donkey sera also gave comparable growth of T. annulata infected cells in vitro. Successful use of heterologous sera greatly helped in reducing the cost of in vitro cultivation of T. annulata schizonts. These findings have important implications on mass production of an attenuated cell culture vaccine for the control of bovine tropical theileriosis.


Recovery from rheumatoid cerebral vasculitis.
A 48-year-old woman with the classical features of longstanding rheumatoid arthritis acutely developed a diffuse cerebral disease. Angiograms showed extensive cerebral vasculitis, and CT scan demonstrated cerebral oedema and haemorrhage. Her clinical state, EEG and CT scan rapidly returned to normal following treatment with corticosteroids.


Genetic and antigenic heterogeneity of different parapoxvirus strains.
Six stomatitis papulosa and three Orf virus strains were compared by serology and by DNA restriction analysis. A neutralization kinetic study revealed extensive serological cross-reactivity between all strains, but did not allow their classification. Restriction analysis of viral DNAs revealed two distinct groups among the stomatitis papulosa strains while the Orf virus strains formed a third, more heterogeneous group. The large heterogeneity of restriction patterns of parapoxvirus DNAs as compared to those orthopoxviruses is discussed.


The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.
HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and that are harnessed to efficiently interact with mucosal barriers exposed during sexual intercourse. Several cofactors contribute to semen infectivity and may enhance the risk of HIV-1 transmission to a partner by increasing local HIV-1 replication in the male genital tract, thereby increasing the number of HIV-1-infected cells and the local HIV-1 shedding in semen. The introduction of combination antiretroviral therapy has improved the life expectancy of HIV-1 infected individuals; however, there is evidence that systemic viral suppression does not always reflect full viral suppression in the seminal compartment. This review focus on the role semen leukocytes play in HIV-1 transmission and discusses implications of the increased resistance of cell-mediated transmission to immune-based prevention strategies.


Nonculture methods for diagnosing chlamydial infection in patients with trachoma: a clue to the pathogenesis of the disease?
We studied five different tests for diagnosing conjunctival Chlamydia trachomatis infection in specimens obtained from 100 children with moderate-to-severe trachoma. The tests were Giemsa stain, isolation in cell culture, direct fluorescein-conjugated monoclonal antibody, enzyme immunoassay, and a DNA probe. The Giemsa stain was least sensitive at 29%. The other tests gave essentially equivalent performances: sensitivity ranged from 73% to 84% and specificity from 93% to 100%. Seven of the 45 positive specimens were only positive in cell culture, whereas 11 of the 45 were negative in culture but positive in at least two nonculture tests. We speculate that these discordant results actually reflect the biologic status of the chlamydial infection. There appears to be a stage in the infection where chlamydial antigens and nucleic acids can be detected in the absence of infectivity. This stage of infection may contribute to the pathogenesis of trachoma by providing a source of sensitizing antigen.


Relationships among the cell cycle, cell proliferation, and aryl hydrocarbon receptor expression in PLHC-1 cells.
Aryl hydrocarbon receptor (AHR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause altered cell proliferation in many tissues in vivo and cell types in vitro, and the AHR has been suggested to play a role in cell cycle regulation in mammalian systems. However, the mechanisms underlying these effects are poorly understood. The overall objective of the present work was to investigate possible interactions between cell proliferation, the cell cycle, and AHR signal transduction in a piscine system, the PLHC-1 cell line, which is being used increasingly in aquatic toxicological research. The specific objectives were to characterize proliferation rates and the cell cycle in these cells, to measure effects of TCDD on cell proliferation, and to determine if expression of the AHR varies during the cell cycle. The doubling time of PLHC-1 cells was determined to be 22 h, and the durations of the G1, S and G2/M stages of the cell cycle were 13, 3, and 6 h, respectively. A minimum seeding density of 1.2 x 10(5) cells/cm(2) in medium with 10% calf serum and 0.3 x 10(5) cells/cm(2) in 10% fetal bovine serum was found to be required for subsequent proliferation. Of several cell cycle inhibitors tested, only aphidicolin and nocodazole were effective for obtaining synchronous cell populations. TCDD was found to inhibit PLHC-1 cell proliferation in a time- and dose-dependent manner in multiple passages of one sub-clone, but not in several other sub-clones. Neither AHR mRNA nor protein expression varied during the cell cycle, as measured by RT-PCR and specific binding of [(3)H]TCDD in synchronous PLHC-1 cells. This work establishes techniques for identifying and characterizing possible interactions between the cell cycle and AHR signal transduction in PLHC-1 cells. Taken together, the results indicate that PLHC-1 cells are amenable to analysis of AHR-cell cycle interactions, but that heterogeneity of sub-clones may complicate their use for investigating AHR-mediated changes in proliferation.


[Hand fine motor skills and use of both hand and arm in subjects after a stroke: a systematic review].
In clinical practice it is important to be able to assess the function of the upper limb of the patient who has suffered a stroke. There is currently no systemic review that could identify assessment tools for the 'fine use of the hand' and 'use of both hand and arm'. Primary, to identify observational tools which can assess the fine use of the hand and the use of both hand and arm in patients with stroke sequels. Secondary, to analyze the bias risk in the included articles, describing and categorizing the clinical utility, validity and reliability. A search was carried in Medline, LILACS, SciELO and Open Grey, which included articles published until October 2015. Studies that validate assessing tools of the upper limb in subjects with a stroke sequel which evaluate the fine use of the hand and the use of both hand and arm were included. Eleven tools in evaluate observational haven been selected, which assess the fine use of the hand and the use of hand and arm. In every case both validity and reliability have been reported, but clinical utility has been less considered for assessment. The studies that researched these tools showed a high risk of bias in their development. ARAT-19 showed a lower bias risk, but when it has to do with applicability and the reference trial is taken into account, the level of concern is high.


Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells.
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC‑27 and MKN‑45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma‑associated oncogene (Gli)‑1, Gli‑2 and Gli‑3 were examined using western blot and reverse transcription‑quantitative polymerase chain reaction analyses. RNA interference was used to detect whether the effects of metformin treatment on the Shh signaling pathway were dependent on AMP‑activated protein kinase (AMPK). The results revealed that the protein and mRNA levels of Shh and Gli‑1 were decreased by metformin treatment in the two cell lines in a dose‑ and time‑dependent manner. Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli‑2 and Gli‑3. The small interfering RNA‑induced depletion of AMPK reversed the suppressive effect of metformin on recombinant human Shh‑induced expression of Gli‑1 in HGC‑27 gastric cancer cells. Therefore, metformin inhibited the Shh signaling pathway in the gastric cancer cell lines and the inhibitory effect of metformin on the Shh pathway was AMPK-dependent.


Targeting of the innate immunity/inflammation as complementary anti-tumor therapies.
Different types of cancer take advantage of inflammatory components to improve their life-span in the organs. A sustenance of growth factors and cytokines (e.g. interleukin (IL)-1, tumor necrosis factor, IL-6, vascular endothelial growth factor) supports malignant cell progression and contributes to suppress the body immune defense. Strategies to modulate the host micro-environment offer new approaches for anti-cancer therapies. For these reasons new molecules with anti-tumor and anti-inflammatory features (e.g. trabectedin) are looked at with new eyes in the light of the crucial link between inflammation and cancer.


Tactile function of educable mentally retarded children.
The tactile perception ability of 29 seven-and eight-year-old educable mentally retarded children was evaluated by using the tactile perception portions of the Southern California Sensory Integration Tests. The children were also observed for tactile defensive behavior. Compared to normal children of the same age (as reported in normative data), this sample of children was significantly inferior in manual form, finger identification, graphesthesia, and perception of simultaneous stimuli, but not in the localization of single stimuli. During the testing, 62 percent showed tactile defensive behavior. The role of tactile perception in the development of symbolic communications is reviewed.


Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis.
The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.


[Pharmacological fMRI : new possibilities for assessing the efficacy of analgesic agents].
Pain is a complex subjective phenomenon that so far cannot be objectively quantified by any standardized procedure. This fact renders it also difficult to measure the efficacy of analgesic drugs. In recent years the application of functional magnetic resonance imaging (fMRI) has significantly increased our current knowledge about the brain physiological correlates of pain in humans. The technique is non-invasive and detects the increased blood flow into neuronally active brain regions based on the so-called BOLD (blood oxygenation level dependent) effect of T2-weighted MRI. This paper gives an overview of the application of pharmacological fMRI (phfMRI) as an approach to evaluate the efficacy of analgesics. In contrast to EEG- and MEG-based methods phfMRI allows more flexibility in the design of experimental paradigms and stimulus protocols to account for the diversity of clinical pain types (inflammatory pain, tactile allodynia etc.) or their dependence upon psychological circumstances (anxiety, depression, stress) in which pain occurs. However, in order to specifically refer results from phfMRI to the neuronal processes underlying pain, future research needs to increase the understanding of the mechanisms underlying the neurovascular coupling reaction represented by the BOLD technique. The same applies for the influence of cerebrovascular diseases on the BOLD response.


Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis.
Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED. We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0. A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil. Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.


QSPR using MOLGEN-QSPR: the example of haloalkane boiling points.
MOLGEN-QSPR is a software newly developed for use in quantitative structure property relationships (QSPR) work. It allows to import, to manually edit, or to generate chemical structures, to detect duplicate structures, to import or to manually input property values, to calculate the values of a broad pool of molecular descriptors, to establish QSPR equations (models), and using such models to predict unknown property values. In connection with the molecule generator MOLGEN, MOLGEN-QSPR is able to predict property values for all compounds in a predetermined structure space (inverse QSPR). Some of the features of MOLGEN-QSPR are demonstrated on the example of haloalkane boiling points. The data basis used here is broader than in previous studies, and the models established are both more precise and simpler than those previously reported.